Lupo G, Anfuso C D, Assero G, Strosznajder R P, Walski M, Pluta R, Alberghina M
Department of Biochemistry, Faculty of Medicine, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Neurosci Lett. 2001 May 11;303(3):185-8. doi: 10.1016/s0304-3940(01)01749-9.
We describe the inhibitory effect of full-length Abeta(1-42) and Abeta(25-35) fragment of amyloid-beta peptide on phosphatidylcholine (PtdCho) metabolism in bovine retina capillary pericytes. Cell cultures were incubated with Abetas for 24 h. Peroxidation indices (malondialdehyde and lactate dehydrogenase release) significantly increased after 20-50 microM Abeta(1-42) or Abeta(25-35) treatment. In addition, [Me-3H]choline incorporation into PtdCho strongly decreased while either 3H-choline or 14C-arachidonic acid release from prelabeled cells increased, indicating PtdCho hydrolysis. The effect was very likely due to prooxidant action of both Abeta peptides. Reversed-sequence Abeta(35-25) peptide did not depress 3H-choline incorporation nor stimulate PtdCho breakdown. With addition of Abetas at low concentrations (2-20 microM) to pericytes, marked ultrastructural changes, well connected to metabolic alterations, emerged including shrinkage of cell bodies, retraction of processes, disruption of the intracellular actin network. Cells treated with higher concentrations (50-200 microM) displayed characteristics of necrotic cell death. The data suggest that: (a) Abeta(1-42) and Abeta(25-35) peptides may modulate phospholipid turnover in microvessel pericytes; (b) together with endothelial cells, pericytes could be the target of vascular damage during processes involving amyloid accumulation.
我们描述了淀粉样β肽的全长Abeta(1 - 42)和Abeta(25 - 35)片段对牛视网膜毛细血管周细胞中磷脂酰胆碱（PtdCho）代谢的抑制作用。将细胞培养物与Abetas孵育24小时。在20 - 50 microM的Abeta(1 - 42)或Abeta(25 - 35)处理后，过氧化指标（丙二醛和乳酸脱氢酶释放）显著增加。此外，[Me - 3H]胆碱掺入PtdCho的量大幅下降，而预标记细胞中3H - 胆碱或14C - 花生四烯酸的释放增加，表明PtdCho发生水解。这种效应很可能是由于两种Abeta肽的促氧化作用。反向序列的Abeta(35 - 25)肽既不抑制3H - 胆碱掺入，也不刺激PtdCho分解。在周细胞中添加低浓度（2 - 20 microM）的Abetas后，出现了与代谢改变密切相关的明显超微结构变化，包括细胞体收缩、突起回缩、细胞内肌动蛋白网络破坏。用较高浓度（50 - 200 microM）处理的细胞表现出坏死性细胞死亡的特征。数据表明：(a) Abeta(1 - 42)和Abeta(25 - 35)肽可能调节微血管周细胞中的磷脂周转；(b) 与内皮细胞一起，周细胞可能是淀粉样蛋白积累过程中血管损伤的靶点。
